Method of producing organic mercurials



Patented Aug. 19, 1952 METHOD OF PRODUCING ORGANIC MERCURIALS Frank J. Sowa, Cranford, N. J.

No Drawing.

Application May 15, 1946,

Serial No. 670,016 14 Claims. (01. 260-433) My invention relates to methods for producing aromatic mercurials and to new chemical compounds produced by suchmethods as well as new compositions and uses for such compounds.

It is well known that many aromatic mercurials have valuable fungicidal and bactericidal properties and are useful for other purposes. Most of those compounds in common use today have the general formula R-HgX in which R is a roup containing an aromatic nucleus having mercury attached to a carbon atom of the ring, and X is an anion. However, many aromatic mercurials having other formulas are valuable fungicides or have antiseptic or germicidal properties and can be produced in accordance with my invention.

Various methods have been employedheretofore for producin aromatic mercury compounds havingthe general formula R-Hg--X, but they have in almost every case involved the formation of an acetate compound by reactions between mercury oxide and acetic acid or-betweenmercuric acetate and aromatic compounds. Some aromatic mercurials have also been produced by thermal decomposition reactions. However, such methods havebeen prolonged and diificult to control whereas plenylmercury acetate and similar compounds are expensive and many compounds which contain a substituted phenyl group cannot be produced from phenylmercury acetate or by other methods of the prior art. Moreov r, many of these compounds have corrosive properties or are irritating to the skin and therefore cannot be handled readily or without danger.

In accordance with my invention novel methods of producing aromatic mercurials are pro.- vided wherein. direct reaction takes place between mercuric sulfate and aromatic compounds in the presence of sulfuric acid. Y The reactions are carried out readily and frequently take place at relatively low temperatures so that theycan be easily controlled and do not require special or expensive equipment foriproducing the products, Moreover, the cost of the materials employed and the time and cost of conducting the reactions render the process relatively economical. Fur-v thermore, many new aromatic mercury com-. pounds can be produced in accordance with the present invention and compounds which do not produce irritation or inflammationin contact with the skin are readily manufactured.

One of the objects of my invention isto re.-. duce the cost of producing aromatic mercurials.

Another object of my invention is. to produce new aromatic mercurials. H

A further object of my invention is to provide novel and economical methods adapted for use in producing awvide variety of aromatic mercurials. l

A specific object of my invention is to produce aromatic mercurials by reaction between aromatic compoundsand mercuric sulfate in the presence of sulfuric. acid.

These and... other objects and features of my invention "will appear. from. the following description. thereof in which reference is made to specific and preferred methods of procedure and compositions for the purpose of indicating the nature of myinvention, but without intending to limit the scopeof my invention.

In carrying out reactions embodying my invention a solution of mercuric sulfate in sulfuric acid is employed. For most economical procedure mercury is dissolved. in sulfuric acid to produce a solution containing mercuric sulfate dissolved in sulfuric acid. However, mercuric oxide (HgO) .or mercuric sulfate (HgSOa) may be dissolvedin sulfuric acid to produce solutions containing mercuric sulfate and sulfuric acid adapted for use in accordance with my invention.

Typical solutions of this characterhave been producedas follows:

Example I grams of mercury and grams of concentrated sulfuric acidwere boiled forv one hour and .a half with vigorous evolution of sulfur dioxide. The solution was then diluted with 1000 cc. of water at which time it turned slightly yellow. A small amount of sulfuric acid was addedto produce a clear solution and the solution was then filtered. About two'gramsof undissolved white material, presumably mercurous sulfate, was then filtered off leaving a yellow colored solution suitable for use in conducting further reactions in accordance with my invention; The reactions which take place require the expenditure of one mol of sulfuric acid to convert the mercury into mercuric oxide with therelease of sulfur dioxide. A second mol of the sulfuric acid'is expended in converting the mercuric oxide to mercuric sulfate. The final reagent therefore contains approximately two mols of free sulfuric acid for each mol of mercuric sulfate in the solution.

Example II .4 moles of technical concentrated sulfuric acidwere added to 1 mole of-mercur i'c' oxide and. the mixture heated 'until all of the solid was white. The mixture was then added solution. The solution was filtered through di ether and dilute acids but readily soluble in dilute caustic soda and aqueous solutions of triethanolamine and mixtures containin ammonium hydroxide and ammonium 1actate. On heating the reaction product it was unchanged at 235 C. but turned pink as the temperature was increased and was a dark brown at 290 C.

In order. to determine :the composition and structure of this mercury derivative of salicyclic acid more fully, the product was treated with iodine dissolved in methyl alcohol and the re- .sulting product was extracted and found to melt I have discovered that solutions of this character react readily with aromatic compounds 'to produce aromatic mercurials.

In someinstances.

the reaction mixture is heated or even refluxed substantially at room temperature. ucts Obtained in many cases have thegeneral formula R-I-Ig-SO4H in which R represents a group'containingan aromatic nucleus which may or may not besubstitutedandwhich has the mercury attached to a carbon atom of the ring. However, other salts or compounds can beproducedby replacement of the sulfateradical by hydroxyl, acetate, lactate, nitrate, chloride or other anions. This is usually'accomplished by neutralizing the excess -sulfuri'c. .acid employed in the reaction with sodium hydroxide to .produce the corresponding, hydroxide. The desired salts can then be produced from thehydroxide by treatment with :an .acid or in any conventional orpreferred manner.

l 0thercompounds produced in accordance with my invention appear :to be "mercury containing inner-anhydrides :of .aromatic. acids whereas various polymercurials {also can be produced by themethods .of :my invention.

.Thearomatic compounds .used in carryingout thereactions are preferably :derivatives of benzeneor' its homologues, or oxygen :containing iderivatives .of benzene ;-such as' carboxylic compounds, :ethers, phenols-and esters. Typicalof these compounds areshydrocarbons such as benzene and toluene; substituted'hydrocarbons.such as chlorbenzene, aniline and .dimethylaniline; carboxylic acids such as benzoic.and-salicylic acids; .phenols and cresols; aromatic etherssuch as 'anisole and amyhphenylether; aromatic .alcohols' such .as be'nzyl a-lc'ohol andoxides such :as diphenyloxide. It thus appears that substantially 'any aromatic compound can be usedin conducting reactions embodying mykinvention and many-new compounds not her'etoforeproduced can be manufacturedreadily andteconomically-thereby. Y r

In order to indicate vthenature ofmyinvention more fully the following specific examples: of reactions betweenthe :solutions of i-ExamplesI or II and various organic -:compounds are cited as representative of :the many'reactionsvvhich can bewarried out and -:astypica1 of theicompounds tion of Example I were'then addedin small proportions while'the mixture was maintained at its boiling :point.- The mixture was thoroughly shaken after each addition of th mercuriclsulfate. Precipitation occurredrapidly yielding 73 grams of a whitescrystalline substance-which is substantially insoluble in water, benzene,. alcohol,

The prod whereas in other cases the reaction takes place.

at '230 C. with slight decomposition. This is the -known melting point of 4 -iodo sallcyclic acid A sample of this :(Chemical Abstracts 221 959) .iodo acid wasfurther reacted with acetic anhy- .drideiand gave a product which melted sharply at 156-1 5? C. corresponding to the known melting .point of 4-iodo aspirin (Chemical Abstracts 1811657). It is therefore concluded that the product obtained ':by reaction-between salicyclic acid andmercuric sulfate in Vthe;presence of sulfuric :acid has-the; structural formula Example IV.-12.2grams smole) of benzoic acid were dissolved in slightly more than "the minimum amount of boiling Water necessaryzfor solution. The mercuric sulfate: solution of :Example I was added slowly while refluxingthe mixture. Precipitation occurred almost immediately, resulting in I the formation ;of 25.1 .grams of :a white crystalline :product. This compound decomposes at temperatures .above, about 305 C. without'melting. It is substantially insoluble in Water, alcohol ether -andbenzene,-butais readily soluble in;sodium-hydroxide and aqueous solutionseof triethanolamine. p

=It-is-believed that'thisyprorduct is largelyrinthe form .of an inner-anhydride :Of the acid LD'IOdlJCGd according-to the-equation I This isconfirmedby quantitative analysis and'is consistent *with 'the =react'ions described in Helvetica '"Ghemica -Acta vol. 38, page 1'7 (-1945). Furthermoraas pointed out-inExampleXIL-the mercury is j-evidently-present in the compound-pin a positionortho -'to the *ca'rboXy1 group.

Ea'ampl'e 'V-.3-50 ccsof the mercuric sulfate solution of Example Iwere added to' 10-.8 grams 61 6 F mole) of' anisoleand themix-ture shaken periodically whilemaintainedat'room' temperature. *In about 1 5' -m'inutes precipitationbegan and "continuedfor -'several hours, the -rnixture being shaken frequently. 1 The resulting product was'a white T crystalline material which on heatingbeginsztotturn brown at about -170 C., but doesnot melt even.at'310 C. "This produc-twas difiicultto dry and. when zallowed to remain wet from thesolution ithe ficrystals lturn pink on standing in air. However, 'when washed with .ethyl alcohol or with benzene or when-suspendedin methanol and then washed theyremaine'd white indefinitely.

inzthe open air.- 1

The composition and structural formula of theanisole-mercuric acid sulfate reaction product was determined by treatment with iodine inal-r coholic solution, whereby a product melting at.

66.5 C. was obtained corresponding to the melting point of 2,4,di-iodo-anisole (Beilstein vol, 6,.

page 210). It is therefore concluded that the product is a polymercurial having the structural.

formula Example VI .,-500 cc. of .the fmerciirie sulfate solution of Example I were added toa solution of 18.8 grams of phenol in 300' ccf of'water]; The mixture was agitated and precipitation took. place within about one-half hour while the reaction:

mixture was maintained at room temperature. Precipitation continued .to take place over a period of several hours, yielding a white crystalline product which on heatingto200 C. begins to turn pink and 'is brown. incolor 'at. 280' C.

although no melting was observed. .When'treate'd' with iodine the iodine compound of the reaction productwas found to meltat 5i" C. to 157? C.

which corresponds to the known meltin poin't of 2,4,6 iodo-phenol. It is therefore concluded that the reaction product produced in accordanc with my invention has the structural formula H O l HSO4Hg- -HgS 04H I HES 04H. 7

Example VII.10.8 grams mole'Ybfbehzyl alcohol were mixed with 250 cc. of the mercuric sulfate solution of Example II. The mixture was shaken frequently while maintained at room temperature. A precipitate was produced on standing overnight and consisted of a White crystalline product which is easily dried and flaky in character and which decomposes without melting at temperatures in the neighborhood-of 300 C.-' The structural formula of this product has not been determined, but it is believed to be a benzyl alcohol mercury acid sulfate having a composition corresponding to th formula HOCH2CeH4HgSO4I-I' Other reaction products Product which. decomposes at temperatures be tween 280 and 300 C. without melting; I

e u e ppl m rcu ie Example -X.,-The product pro d. bYzIZ 'Q-T tions et een ni ne; an mercur c a id. sul ate solutions .is white in color butturns yellowwhen; .heated to 140 C. and is completely decomposed;

at 198 C. 0n iodination of the reaction product.

a compound melting at 186C. to. 187 C..,is-ob-s tained which corresponds to the melting point of 2,4,6 iodo-aniline as given by Beilstein. It is therefore believed that the aniline reaction product has the structural formula A white. crystalline product by reactions between mercuric sulfate and dimethyl-.

aniline in the presence of sulfuric acid.

. Example XI.-:+Products have also been obtained v by reactionsbetween the mercuric sulfate. solutions-of Examples I and II and benzene, toluene, and i'chlorbenzene. These reactions require continuedand vigorous agitation because th reactantsxare not miscible and intimate contact is not readily maintained. In each case the product obtained was a white crystalline substancewhich when heated turns dark or decomposes without melting. :The compositionrof the benzene reac,-. tion product has not been definitely determined but: its melting point and reactions differ from those of phenylmercury sulfate produced by reactionsbetween phenylmercury hydroxide and.su1-..-: furic acid. It is believed to .be a polymercuriaL;

The toluene and chlorbenzene reaction products also appear to be polymercurials. ..1

. In general the oxidation compounds of benzene and itsrlerivatives react .most readily with mer curic sulfate and those compounds containing the group OR attached to a carbon atomof the ring, where R is hydrogen or an a1kyl"or..-ary1.

group, are formedat room temperatures The concentration of the mercuric sulfate-sulfuric acid solution also has some influence on thespeed and-optimumreaction conditions. Thus, when using cc. of the-solution of Example I diluted with 900 cc. of water to form 1 liter of the reaction solution it was found that the speed-of the .reaction was slower and some heating :was

desirable to produce the reaction products rapidly.:

' Other aromaticjcompoand's *Productsresulting from reactions between aromatic' compounds and mercuric sulfat'e sulfuric' acid solutions are readily converted into other produces the corresponding aromatic mercury hydroxide, followed by treatment with an acid to: produce" the desired salt.

"Example XII The' product of Example IV can be' converted into the corresponding mercur chloride "by the addition of potassium chloride to a solution of; the product in sodium hydroxide.

The chloride'produce'd is a white crystallinema terial which is sintered and begins to turn brown at;about 2;60,' but itis not fully inelted at 310 alfsiinilarproducti s produced by precipitation with hydrochloric acid from a sodium hydroxide solution of the product of Example IV.

. In order todetermine the composition and formula of' the chloride, the compound was treatedwith, iodine. dissolved in boiling methanol, pro

ducing areaction product which had a melting point of 161162 C. which correspondsto the known melting point:of ortho 'iodo benzoicpacid.

salts by treatment with sodium hydroxide, which The compound istherefore' believed to have the followings'tr-uctural forniula l 1 I r. ,--'.l.' I I Example XIII .--15.8 grams of the salicylic acid 7 reaction product of Example III were dissolved in dilute sodium hydroxide in which it is readily soluble and filtered through diatomaceous earth,

edtoturncolor at.about.225 .C. and was-dark brown at1260 C.

Example XIII.-"Ihe benzoic acidreactionproductof Example IV c'anhe converted into thecorresponding :acetate by the addition of glacial. acetic acid :to a solution of the reaction product inL-sodium hydroxide, .usin-g .suficient acetic .acid torender thesolution strongly acid. IYheacetate. is a;v white: crystalline product whichbeings to. decomposetat. about. 290 0. without melting.

From the wide varietyof aromatic. compounds: whichhaye been produced. and .tested, it.;wi1l1be apparent that .my invention .is adaptedior use in producing .a great variety of aromatic. mercury many of which have not been produced: heretofore. In view thereof it. should .be understood. that the..-examples cited-above are in;- tended to be ilhistrative only and are not intendeditoilimit the scope of my invention.

,Products producedin accordance withmy in.- venticn possess valuable fungicidal. and bactericidal properties asiindicated .by the fact thateach of the: products. described. above produces -a.-.pronounced halo when applied to culturesof. Aspargillus m'gerfandStaphylococcus,aizreus, using the procedure of the Food and Drug Administration Ager Plate Test No. 198. They may be dissolved in various aqueous solvents for use in textile treating baths. or for agricultural sprays or other purposes .usingmethods set forth in my copendingapplications .Serial Nos. 489,244; .500,449 new Patent Nos. 2,411,815 and 2,432,262, respectively and 518,475 now abandoned. In the alternative. they may be used i'na dry powered form or when mixed with diluents or other agents for .many purposes such as seed disinfectants .or theflikeras indicated for example by U. S. Patent .No. 13618369. Products of the present invention also be'var-ied in many respectswithout departingfrom 'the spirit and scope of my invention.

Iclaima' l. "Themethod of producing an aromatic-mer- 8 cury acid. sulfate which comprises contacting an. aromatic compound with an aqueous solution. containing mercuric sulfate and sulfuric acid. in theproportion of about onemole. of mercuric sulfate for atfileastv two'moles of. sulfuric acid present? :U

2. The method of producing an aromatic mercury acid; sulfate which comp'risescontacting an aromatic: compoundawith an aqueous solution con taining. mercuric sulfate. and sulfuric acid in. the proportion of about one mole of mercuric sulfate; and at least two moles of sulfuric acid for each 1500 cc. of water in the solution.

3. The method. of producing aromatic mercury acid sulfate which comprises contacting an oxygen containing derivative of benzene selected from the 'groupjconsisting of. aromatic acids, phenols, aromatic-alcohols and aromatic ethers with a solution containing about onemol of mercuric sulfate fornot less than two mols of sulfuric acid present in the solution.

4. The method of producing, an aromatic mer-fv cury'acid'sulfate which comprises contactingan aqueous solution containing about one mole of mercuric sulfate for each two mols offsulfuric acid with an aromaticcompound' containinga' benzene "ring to a carbon atom of which attachejd a group represented by the'lradical -goli where'R is selected from the group consistingiof hydrogenyalkyl and aryl. E 5. A composition of'matter having thestructural formula (IDOOH ngsoila 6. A composition of matter having the structural formula n s olu tural' fo m a present wtli ben'zoic acid. p a

10.-The method of producinganiscle-mercury acid -s ulf ate which comprises contacting ousksolution oritaihihg-about-foii moi Y 7 cur-i'csul fate for; each two moleso J u fur 0 acid present with anisole.

la-0H 14. A compound having the composition represented by the formula and consisting of a white crystalline product which is flaky in character and which decomposes without melting at temperatures in the neighborhood of 300 C.

FRANK J.'SOW'A.

REFERENCES CITED The following references are of record in the file of this patent:

10 UNITED STATES PATENTS Number Name Date 1,525,078 Kropp Feb. 3, 1925 1,604,778 Klages Oct. 26, 1926 1,613,569 Sagi Jan. 4, 1927 1,618,095 Klages Feb. 15, 1927 1,748,331 Englemann Feb. 25, 1930 1,782,090 Copley et al Nov. 18, 1930 1,787,630 Kharasch Jan. 6, 1931 1,862,896 Kharasch June 14, 1932 2,014,676 Weed Sept. 17, 1935 2,044,959 Tisdale June 23, 1936 2,353,312 Kobe et a1. July 4, 1944 2,376,291 Sowa May 15, 1945 2,392,801 Peterson Jan. 8, 1946 2,543,733 Sowa et a1 Feb. 27, 1951 FOREIGN PATENTS Number Country Date 22,336 Great Britain May 23, 1907 242,669 Great Britain Feb. 11 1926 119,228 Switzerland Mar. 1, 1927 OTHER REFERENCES Organic Compounds of Mercury Whitmore (1921), page 217. I

Rupp et al., "Archiv der Pharmazie, vol. 265 (1927) pages 323-331.

Chemical Abstracts, vol. 21 (1927), page 1867.

Pesci, "Gazzetta chimica italiana, vol. 28, pt. 2 (1898). page 466. V

Goddard et al., Textbook of Inorganic Chemistry, vol. XI, pt. I, (1928) pages 116-117. 

1. THE METHOD OF PRODUCING AN AROMATIC MERCURY ACID SULFATE WHICH COMPRISES CONTACTING AN AROMATIC COMPOUND WITH AN AQUEOUS SOLUTION CONTAINING MERCURIC SULFATE AND SULFURIC ACID IN THE PROPORTION OF ABOUT ONE MOLE OF MERCURIC SULFATE FOR AT LEAST TWO MOLES OF SULFURIC ACID PRESENT. 